ABSTRACT Support is requested for a Keystone Symposia conference entitled Atherosclerosis: Lessons Learned and Concepts Challenged, organized by Drs. Laura F. Michael, Gerard Pasterkamp and Sekar Kathiresan. The conference will be held in Taos, New Mexico from February 4 - 8, 2018. Atherosclerosis is a chronic, systemic disease process whereby fatty deposits, inflammation and fibrosis accumulate in arterial vessel walls. Organs systems, including heart, brain, kidneys, as well as extremities can be damaged leading to atherosclerosis-driven clinical outcomes. According to the American Heart Association, 15.5 million Americans have coronary heart disease of which 7.6 million experienced myocardial infarction. These statistics are reflective of global incidence. Treatment of atherosclerosis often begins with robust cholesterol-lowering treatments, yet many patients continue to experience cardiovascular events. Recent attempts to provide cardiovascular protection to such patients have included anti-inflammatory and HDL-raising therapeutic approaches that have yielded little benefit. Building knowledge of atherosclerosis disease etiology, defining unique attributes of patient differences as simple as sex or genetic inheritance, and using technology to identify patients with early disease is foundational for the scientific community to develop urgently needed therapeutics. The current concept of acute coronary syndrome (?the vulnerable plaque?) and widely applied animal models are debated because clinical presentation, underlying pathology and pathogenetic mechanisms are subject to change due to improved medical treatment. The goals of this meeting are to: 1) Challenge current dogma of atherosclerosis etiology and explore intra-organ cross-talk that may underlie disease evolution; 2) Consider emerging risk factors and their origins as intervention targets; and 3) Explore cutting- edge technologies to discover new therapeutic targets and approaches for drug development. By bringing together scientists from preclinical to clinical settings and from industry to academic institutions, this conference will nurture discussions to translate breakthrough discoveries into therapeutics.